1. Field of the Invention
The present invention relates to the treatment of allergies. Allergic disorders affect as many as one in four Americans (59,000,000). More than 17% have upper respiratory allergies, including hay fever. Another 4% have asthma, and 10% have allergic skin conditions such as eczema and other rashes. It is estimated that some 40,000,000 school days are lost yearly because of asthma, in addition, approximately 6,000 lives are lost to asthma, and dozens die of insect bites, annually. The accepted allergy treatment method is hyposensitization injections containing minute amounts of allergens causing the reaction, given in incremental doses once or twice weekly until symptoms improve, and then maintained at a set dosage with decreasing frequency for approximately three years. If carefully selected, approximately one-third of patients find their symptoms are relieved substantially by this therapy. The rest have mild to moderate improvement. This immunotherapy method has been standard practice since 1911. The present invention provides a method of immunotherapy and a modified allergen extract and a method of making the modified allergen extract.
2. Description of the Prior Act
Modified allergen extracts for use in immunotherapy have been reported in the literature. Such extracts have been modified with the desire to reduce their allergenicity without sacrificing immunogenicity and hence achieve improved immunotherapy results with fewer injections. Polymerized grass pollen allergens have been prepared and tested in immunotherapy. See, Patterson et al., "Polymerization of Individual Species of Grass Pollen Allergen", J. Allergy Clin. Immunol 72:129-133, (1983); Fitzsimons et al., "A comparison of the Immune Response to Immunotherapy with Polymerized Grass Allergen and Monomeric Grass Allergen"; Annals of Allergy 57:291-294 (1986); Fitzsimons et al., supra reports that polymerized and monomeric grass pollen extract give comparable result in immunotherapy. Further reports have suggested that the polymerized grasses contain an increased amount of immunity producing allergen. It has been reported that in use a series of fifteen (15) injections with the polymerized pollen are as effective as a series of seventy (70) standard injections. Modified allergens for allergy desensitization have also been prepared by treating pollen extract with formaldehyde. Such formaldehyde treated allergens are referred to as "allergoids". Polyethylene glycol modified ragweed extracts have also been proposed for use in immunotherapy. See Juniper, et al. "Polyethelene Glyco - Modified Ragweed Extract: Comparison of Two Treatment Regimens". J. Allergy Clin Immunol 78: 851-6 (1986). See also U.S. Pat. No. 4,180,562 (Patterson) which discloses the use of ragweed polymerized extracts in immunotherapy.
Other chemically modified allergens have been suggested in the art.
The following summarizes the types of chemically modified allergens and their modes of action.
TABLE 1 ______________________________________ CHEMICALLY MODIFIED ALLERGENS Name Treatment Effect ______________________________________ Allergoid Formalin Allergenicity.dwnarw. Antigencity.fwdarw. PER Pyridine Exposed Allergenicity.dwnarw. Antigenicity.fwdarw. Pollinex Glutaraldyhyde- Allergencity.dwnarw. Modified, Antigenicity.fwdarw. Tyrosine-Adsorbed PRW Polymerized Ragweed Allergenicity.dwnarw. Allergens Antigenicity.fwdarw. PEG Monomeric Coupling Enhancement of of Polyethylene T-Suppressor Glycol to Allergen Cells DG-L Conjugation of D- B-Cell Glutamic Acid: Tolerance D-Lysine To Allergen ______________________________________ .dwnarw. = decreased. .fwdarw. = remained unchanged. .uparw. = increased.
From: Perelmutter, L. Lymphocyte Response in Allergic Patients During Immunotherapy in: Allergy-Immunologic and Management Considerations PP. 13-26 Edited by J. T. Spencer, Published by Meded Inc., 1982 Miami, Fla.
See: Marsh DG, Lichtenstein LM, Campbell DH: "Conversion of Group I Rye Pollen Allergen to `Allergoid` by Mild Formation Treatment" Immunology 18:705, 1970.
Furic R, Peremutter L, Goodfriend L: "Modification des Properietes Allergeniques et Antigeniques d'un Extrait d'Ambroisic." Presented at the Fourth International Congress of Immunology, Paris, July 1980.
Patterson R, Suszko J M, Pruzanskv J J, et al: "Polymerization of Mixtures of Grass Allergens." J. Allergy Clin Immunol 59:3l2f, 1977.
Lee W Y, Sehon A H: "Suppression Reaginic Antibodies." Immunol Rev 41:200, 1978.
Katz D H, Homoaka T, Benneceraaf B: "Introduction of Immunological Tolerance in Bone Marrow Derived Lymphocytes of IgE Antibody Class." Proc Natl Acad Sci U.S.A. 70:2776, 1973.